ROLE OF APPENDIX AND GALT IN DEVELOPMENT OF THE PRIMARY HUMAN IMMUNE REPERTOIRE

附录和 GALT 在人类初级免疫库发育中的作用

• 批准号: 6431670
• 负责人: rose G. mage
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6431670
• 关键词: B lymphocyte; antibody formation; autoimmunity; cell differentiation; child (0-11); developmental immunology; gut associated lymphoid tissue; human subject; ileocolonic region; immunocytochemistry; laboratory rabbit; polymerase chain reaction; tissue /cell culture

Our studies in the rabbit have shown that the young appendix is an important site of development of the cells destined to produce protective antibodies. The rabbit appendix has functions similar to those of the avian bursa of Fabricius. In the young rabbit, there is rapid growth and expansion of B lymphocytes in the appendix, and positive and negative selection events occur. We believe that the cells that survive selection in the appendix seed the peripheral lymphoid system and undergo self renewal to maintain the primary repertoire. The data on rabbit led us to study the role of human appendix and GALT in development of the human immune repertoire and mucosal immunity. We compared development of normal human appendix germinal centers (GC) with rabbit appendix GC development at different ages. In both human and rabbit appendix, we found that lymphoid follicles were just beginning to form at birth. Germinal centers became evident at about 1 month in human and at 1 week in rabbit appendix. Most lymphoid development occurred within the first year in the human and within the first 12 weeks in the rabbit appendix. Lymphoid tissue began to atrophy by adulthood in both human and rabbit appendix. The follicles became smaller and fewer in number whereas the connective tissue and smooth muscle increased. The appendix did not entirely involute; germinal centers were still present in 5 human samples from individuals 75 years or older and in 6- and 7 yr-old rabbit specimens. The human appendix shares some characteristics of a "mammalian bursa equivalent"; it is a B-cell rich organ in the young and the morphology of the follicles and GC changes with age. The human appendix is similar in many respects to the rabbit appendix, avian bursa and sheep ileal Peyer's patch, yet several differences exist. The GC structure and relative GC T-cell density of the human appendix throughout development differs from that of the rabbit appendix and chicken bursa which could indicate that human appendix is more similar to a peripheral than central lymphoid organ. However, it is possible that peripheral lymphoid organs share some central lymphoid function. Whether this is true for the human appendix and other GALT warrants further investigation. Molecular studies of sequences of genes encoding antibody heavy and light chain are in progress (see Z01 AI00226-19 LI) to further investigate whether the appendix of man plays any role as a primary lymphoid organ.(J. Dasso et al., 2000).A clinical research protocol (#OH99-I-N026) entitled, "Effect of Appendectomy on Mucosal Immunity in Children" was reviewed and approved by the IRBs of Children's National Medical Center, and NIAID, NIH. I terminated this study as of July 29, 2000 because of low numbers of patients accrued and our inability to carry through the arm of the study that would have analyzed responses to oral polio vaccine. A paper describing the methods developed to prepare and assay patient samples and some preliminary results is in preparation (J. Dasso et al., ms in preparation).

我们在兔子的研究表明，年轻的附录是注定要产生保护性抗体的细胞开发的重要地点。兔附录的功能与Fabricius的鸟囊囊的功能相似。 在年轻的兔子中，附录中B淋巴细胞的迅速增长和扩张，并发生了阳性和负选择事件。我们认为，在附录种子中幸存下来的细胞外周淋巴系统并经历自我更新以维持原发性曲目。关于兔子的数据导致我们研究了人类附录和Galt在人类免疫曲目和粘膜免疫发展中的作用。 我们比较了正常的人类附录生发中心（GC）的发展与不同年龄段的兔附录GC的发展。 在人类和兔子附录中，我们发现淋巴卵泡在出生时才开始形成。生发中心在人类和在兔子附录中为1周的生发中心变得显而易见。大多数淋巴发育发生在人类的第一年内，并在兔附录的头12周内发生。淋巴组织在人和兔附录中成年开始萎缩。 卵泡变小，数量较少，而结缔组织和平滑肌增加。 附录并不完全涉及；来自75岁或6岁和7岁的兔子标本中的5个个体的5个人类样本中仍存在生发中心。 人类附录具有“同等哺乳动物囊囊”的某些特征；它是年轻的B细胞器官，卵泡的形态和GC随着年龄的增长而变化。 人类附录在许多方面与兔子附录，鸟囊和羊皮佩耶的补丁相似，但存在几种差异。 整个发育过程中，人类附录的GC结构和相对的GC T细胞密度与兔附录和鸡囊囊的相差不同，这可能表明人的附录与中央淋巴器官更类似于外围。 但是，外周淋巴器官可能具有某些中心淋巴机功能。 对于人类附录和其他Galt是否正确，需要进一步调查。 正在进行编码抗体重和轻链基因序列的分子研究（请参阅Z01 AI00226-19 LI）进一步研究MAN的附录是否作为原发性淋巴管有任何作用。（J。Dasso等，2000）。由儿童国家医疗中心的IRB和NIAID的IRB批准。 我截至2000年7月29日终止了这项研究，因为累积的患者人数少，并且我们无法通过研究的手臂来分析对口服脊髓灰质炎疫苗的反应。 一篇描述用于制备和分析患者样品的方法以及一些初步结果的论文正在制备中（J. Dasso等人，在制备中MS）。